There are three serotypes of mammalian reovirus (types 1, 2, 3) defined on the basis of neutralizatiob antibodies. These serotypes, when injected into newborn animals, cause different diseases of the central nervous system. Specifically, type 3 causes an acute encephalitis with destruction of neuronal tissue, while type 1 causes a less severe and more indolent disease, attacking ependymal cells and resulting in hydrocephalus. Thus, there is a natural polymorphism of CNS diseases produced by these serotypes. By utilizing genetic hybrid clones between serotypes 1 and 3, it is possible to determine which viral gene(s) is (are) responsible for the biologic properties or reovirus. These hybrid clones will be utilized to define the molecular basis for the differing neurotropism of reovirus. In addition, the role of host cell surface receptors in the pathogenesis of reovirus CNS disease will be studied in vitro utilizing neuronal cell cultures and in vivo by testing inbred strains of mice with genetic differences at the major histocompatibility locus. Furthermore, the host immune response to the different reovirus serotypes will be studied to determine which viral gene products are responsible for eliciting humoral and cell mediated immunity to reovirus and what, if any, is there relation to the virus gene products responsible for the induction of CNS disease. The ability to study the genes products responsible for two different diseases in the central nervous system as well as the host response to the viral infection, offers a previously unavailable avenue for studying the pathogenesis of viral disease.